Hospital admission and mortality rates for non-Covid diseases among residents of the long-term care facilities before and during the pandemic: a cohort study in two Italian regions.

Aim: Long-term-care facility residents are a vulnerable population who experienced reduced healthcare access during the pandemic. This study aimed to assess the indirect impact of the COVID-19 pandemic, in terms of hospitalisation and mortality rates, among this population in two Italian Regions, Tuscany and Apulia, during 2020 in comparison with the pre-pandemic period. Subject and methods: We conducted a retrospective cohort study on people residing in long-term-care facilities from 1 January 2018 to 31 December 2020 (baseline period: 1 January 2018-8 March 2020; pandemic period: and 9 March-31 December 2020). Hospitalisation rates were stratified by sex and major disease groups. Standardised weekly rates were estimated with a Poisson regression model. Only for Tuscany, mortality risk at 30 days after hospitalisation was calculated with the Kaplan-Meier estimator. Mortality risk ratios were calculated using Cox proportional regression models. Results: Nineteen thousand two hundred and fifty individuals spent at least 7 days in a long-term-care facility during the study period. The overall mean non-Covid hospital admission rate per 100 000 residents/week was 144.1 and 116.2 during the baseline and pandemic periods, with a decrease to 99.7 and 77.3 during the first (March-May) and second lockdown (November-December). Hospitalisation rates decreased for all major disease groups. Thirty-day mortality risk ratios for non-Covid conditions increased during the pandemic period (1.2, 1.1 to 1.4) compared with baseline. Conclusion: The pandemic resulted in worse non-COVID-related health outcomes for long-term-care facilities' residents. There is a need to prioritise these facilities in national pandemic preparedness plans and to ensure their full integration in national surveillance systems. Supplementary information: The online version contains supplementary material available at 10.1007/s10389-023-01925-1.

Anti-dementia drugs: a descriptive study of the prescription pattern in Italy.

INTRODUCTION: Acetylcholinesterase inhibitors (AChEIs) and memantine are currently the only anti-dementia drugs (ADDs) approved for treating Alzheimer's disease (AD) in Italy. This nationwide study aims to characterize dementia drug utilization in a population > 65 years, during 2018-2020. METHODS: Different administrative healthcare databases were queried to collect both aggregate and individual data. RESULTS: ADD consumption remained stable throughout the study period (~ 9 DDD/1000 inhabitants per day). AChEI consumption was over 5 DDD/1000 inhabitants per day. Memantine consumption was nearly 4 DDD/1000 inhabitants per day, representing 40% of ADD consumption. The prevalence of use of memantine represented nearly half of ADD consumption, substantially unchanged over the 3 years. Comparing the AD prevalence with the prevalence of ADDs use, the gap becomes wider as age increases. In 2019, the proportion of private purchases of ADDs was 38%, mostly represented by donepezil and rivastigmine. In 2020, memantine was the only ADD with an increase in consumption (Δ% 19-20, 1.3%). DISCUSSION: To our knowledge, this study represents the first attempt to investigate the ADD prescription pattern in Italy with a Public Health approach. In 2019, the proportion of ADD private purchases point out several issues concerning the reimbursability of ADDs. From a regulatory perspective, ADDs can be reimbursed by the National Health System only to patients diagnosed with AD; therefore, the off-label use of ADDs in patients with mild cognitive impairment may partially explain this phenomenon. The study extends knowledge on the use of ADDs, providing comparisons with studies from other countries that investigate the prescription pattern of ADDs.

Reasons for SARS-CoV-2 infection in children and their role in the transmission of infection according to age: a case-control study.

BACKGROUND: The locations where children get exposed to SARS-CoV-2 infection and their contribution in spreading the infection are still not fully understood. Aim of the article is to verify the most frequent reasons for SARS-CoV-2 infection in children and their role in the secondary transmission of the infection. METHODS: A case-control study was performed in all SARS-CoV-2 positive children (n = 81) and an equal number of age- and sex- matched controls who were referred to the S. Camillo-Forlanini Pediatric Walk-in Center of Rome. The results of all SARS-CoV-2 nasopharyngeal swabs performed in children aged < 18 years from October 16 to December 19, 2020 were analyzed. RESULTS: School contacts were more frequent in controls than in cases (OR 0.49; 95% CI: 0.3-0.9), while household contacts were higher in cases (OR 5.09; 95% CI: 2.2-12.0). In both cases and controls, school contacts were significantly less frequent, while on the contrary household contacts seemed to be more frequent in nursery school children compared to primary school or middle/high school children. A multivariate logistic regression showed that the probability of being positive to SARS-CoV-2 was significantly lower in children who had school contacts or who had flu symptoms compared to children who had household contacts. Results showed a 30.6% secondary attack rate for household contacts. CONCLUSION: In our study population, the two most frequent reasons for SARS-CoV-2 infection were school and home contacts. The risk of being positive was 5 times lower in children who had school contacts than in children who had household contacts.

Prevalence and Safety of COVID-19 Vaccination in Community-Dwelling People with Dementia: Findings from a Tertiary Memory Clinic in Italy.

This study aimed to explore the prevalence and safety of SARS-CoV-2 vaccination in individuals with dementia. Patients with mild cognitive impairment or dementia were recruited at a tertiary memory clinic, from March 15 to September 15, 2021. Information on COVID-19 vaccination and adverse events experienced after vaccine administration were collected from caregivers. Two-hundred-seventy subjects were finally recruited. Among them, 253 (93.7%) had received the vaccine and only 69 (27.3%) experienced adverse events. Cognitive and behavioral changes following immunization were only rarely reported. COVID-19 vaccination is safe and well-tolerated in patients with cognitive impairment who should be prioritized in the vaccination campaign.

A single-agent extension of the SIR model describes the impact of mobility restrictions on the COVID-19 epidemic.

Mobility restrictions are successfully used to contain the diffusion of epidemics. In this work we explore their effect on the epidemic growth by investigating an extension of the Susceptible-Infected-Removed (SIR) model in which individual mobility is taken into account. In the model individual agents move on a chessboard with a Lévy walk and, within each square, epidemic spreading follows the standard SIR model. These simple rules allow to reproduce the sub-exponential growth of the epidemic evolution observed during the Covid-19 epidemic waves in several countries and which cannot be captured by the standard SIR model. We show that we can tune the slowing-down of the epidemic spreading by changing the dynamics of the agents from Lévy to Brownian and we investigate how the interplay among different containment strategies mitigate the epidemic spreading. Finally we demonstrate that we can reproduce the epidemic evolution of the first and second COVID-19 waves in Italy using only 3 parameters, i.e , the infection rate, the removing rate, and the mobility in the country. We provide an estimate of the peak reduction due to imposed mobility restrictions, i. e., the so-called flattening the curve effect. Although based on few ingredients, the model captures the kinetic of the epidemic waves, returning mobility values that are consistent with a lock-down intervention during the first wave and milder limitations, associated to a weaker peak reduction, during the second wave.

Antiviral and immunomodulatory interferon-beta in high-risk COVID-19 patients: a structured summary of a study protocol for a randomised controlled trial.

OBJECTIVES: The primary objective of the study is to demonstrate the efficacy of low-dose IFN-ß in reducing the risk of SARS-CoV-2 recently infected elderly patients to progress towards severe COVID-19 versus control group within 28 days. Secondary objectives are: 1) To assess the reduction in Intensive Care Unit (ICU) admission in patients treated with IFN-ß versus control group within 28 days of randomization 2) To assess the reduction in number of deaths in IFN- ß compared to control group (day 28) 3) To evaluate the increase in proportion of participants returning to negative SARS-CoV-2 RT-PCR in IFN-ß -treated versus control group at Day 14 and Day 28 4) To assess the increase in SARS-CoV-2-specific binding antibody titers in IFN-ß compared to control group (day 28) 5) To assess the safety of IFN-ß -treated patients versus control group TRIAL DESIGN: Randomized, Open-Label, Controlled, Superiority Phase II Study. Patients, who satisfy all inclusion criteria and no exclusion criteria, will be randomly assigned to one of the two treatment groups in a ratio 2:1 (IFN-treated versus control patients). Randomization will be stratified by gender. Stratified randomization will balance the presence of male and female in both study arms. PARTICIPANTS: Male and female adults aged 65 years or older with newly diagnosed SARS-CoV-2 infection and mild COVID-19 symptoms are eligible for the study. The trial is being conducted in Rome. Participants will be either hospitalized or home isolated. A group of physicians belonging to the Special Unit for Regional Continued Care (USCAR), specifically trained for the study and under the supervision of the National Institute for Infectious Diseases "Lazzaro Spallanzani", will be responsible for the screening, enrolment, treatment and clinical monitoring of patients, thus acting as a bridge between clinical centers and territorial health management. Inclusion criteria are as follows: ≥ 65 years of age at time of enrolment; Laboratory-confirmed SARS-CoV-2 infection as determined by PCR, in any specimen < 72 hours prior to randomization; Subject (or legally authorized representative) provides written informed consent prior to initiation of any study procedures; Understands and agrees to comply with planned study procedures; Agrees to the collection of nasopharyngeal swabs and venous blood samples per protocol; Being symptomatic for less than 7 days before starting therapy; NEWS2 score ≤2. Exclusion criteria are as follows: Hospitalized patients with illness of any duration, and at least one of the following: Clinical assessment (evidence of rales/crackles on exam) and SpO2 ≤ 94% on room air at rest or after walking test, OR Acute respiratory failure requiring mechanical ventilation and/or supplemental oxygen; Patients currently using IFN-ß (e.g., multiple sclerosis patients); Patients undergoing chemotherapy or other immunosuppressive treatments; Patients with chronic kidney diseases; Known allergy or hypersensitivity to IFN (including asthma); Any autoimmune disease (resulting from patient anamnesis); Patients with signs of dementia or neurocognitive disorders; Patients with current severe depression and/or suicidal ideations; Being concurrently involved in another clinical trial; HIV infection (based on the anamnesis); Use of any antiretroviral medication; Impaired renal function (eGFR calculated by CKD-EPI Creatinine equation < 30 ml/min); Presence of other severe diseases impairing life expectancy (e.g. patients are not expected to survive 28 days given their pre-existing medical condition); Any physical or psychological impediment in a patient that could let the investigator to suspect his/her poor compliance; Lack or withdrawal of informed consent INTERVENTION AND COMPARATOR: Control arm: No specific antiviral treatment besides standard of care. Treatment arm: 11µg (3MIU) of IFN-ß1a will be injected subcutaneously at day 1, 3, 7, and 10 in addition to standard of care. The drug solution, contained in a pre-filled cartridge, will be injected by means of the RebiSmart® electronic injection device. Interferon ß1a (Rebif®, Merck KGaA, Darmstadt, Germany) is a disease-modifying drug used to treat relapsing forms of multiple sclerosis (MS). The dose selected for this study is expected to exploit the antiviral and immunomodulatory properties of the cytokine without causing relevant toxicity or inducing refractoriness phenomena sometimes observed after high-dose and/or chronic IFNß treatments. MAIN OUTCOMES: Primary endpoint of the study is the proportion of patients experiencing a disease progression, during at least 5 days, according to the National Early Warning Score (NEWS2). The NEWS2 score is a standardized approach aimed at promptly detecting signs of clinical deterioration in acutely ill patients and establishing the potential need for higher level of care. It is based on the evaluation of vital signs, including respiratory rate, oxygen saturation, temperature, blood pressure, pulse/heart rate, AVPU response. The resulting observations, compared to a normal range, are combined in a single composite "alarm" score. Any other clinical sign clearly indicating a disease worsening will be considered as disease progression. RANDOMIZATION: Sixty patients will be randomized 2:1 to receive IFN-ß1a plus the standard of care or the standard of care only. Eligible patients will be randomized (no later than 36 h after enrolment) by means of a computerized central randomization system. All patients will receive a unique patient identification number at enrolling visit when signing the informed consent and before any study procedure is performed. This number remains constant throughout the entire study. The randomization of patients will be closed when 60 patients have been enrolled. The randomization will be stratified by sex; for each stratum a sequence of treatments randomly permuted in blocks of variable length (3 or 6) will be generated. BLINDING (MASKING): This is an open-label study. After the randomization, patients will be notified whether they will be in the experimental arm or in the control arm. NUMBERS TO BE RANDOMISED (SAMPLE SIZE): The study plans to enrol 60 patients: 40 in the IFN-ß1a arm, 20 in the control arm, according to a 2:1 - treated: untreated ratio. TRIAL STATUS: Protocol Version: 3.0 Version Date: 18/03/2021 The study is open for recruitment since 16/04/2021.Recruitment is expected to l be completed before 15/08/2021. TRIAL REGISTRATION: EudraCT N°: 2020-003872-42, registration date: 19/10/2020. FULL PROTOCOL: The full protocol is attached as an additional file, accessible from the Trials website (Additional file 1). In the interest in expediting dissemination of this material, the familiar formatting has been eliminated; this Letter serves as a summary of the key elements of the full protocol."

Supporting and Protecting People with Dementia in the COVID-19 Pandemic.

We aimed to explore the awareness and preparedness of dementia caregivers and people with mild cognitive deficits on how to prevent COVID-19 infection and cope with the indirect consequences of the pandemic. A total of 139 patient-caregiver dyads received a telephone survey and 109 completed the survey. The majority of respondents reported having a moderate-to-good knowledge of the typical manifestations of COVID-19. Conversely, only few of them were informed of the atypical presentations and on how to recognize emergency warning signs. Filling the knowledge gaps on COVID-19 in the most vulnerable people may represent a significant resource to tackle the pandemic.

Being the Family Caregiver of a Patient With Dementia During the Coronavirus Disease 2019 Lockdown.

Background: Family caregivers of patients with dementia are at high risk of stress and burden, and quarantine due to the coronavirus disease 2019 (COVID-19) pandemic may have increased the risk of psychological disturbances in this population. The current study was carried out during the national lockdown declared in March 2020 by the Italian government as a containment measure of the first wave of the coronavirus pandemic and is the first nationwide survey on the impact of COVID-19 lockdown on the mental health of dementia informal caregivers. Methods: Eighty-seven dementia centers evenly distributed on the Italian territory enrolled 4,710 caregiver-patient pairs. Caregivers underwent a telephone interview assessing classical symptoms of caregiver stress and concern for the consequences of COVID-19 infection on patient's health. We calculated prevalence of symptoms and regressed them on various potential stress risk factors: caregivers' sociodemographic characteristics and lifestyle, patients' clinical features, and lockdown-related elements, like discontinuity in medical care. Results: Approximately 90% of caregivers reported at least one symptom of stress, and nearly 30% reported four or more symptoms. The most prevalent symptoms were concern for consequences of COVID-19 on patient's health (75%) and anxiety (46%). The main risk factors for stress were identified as a conflicting relationship with the patient and discontinuity in assistance, but caregiver's female sex, younger age, lower education, and cohabitation with the patient also had an impact. Availability of help from institutions or private individuals showed a protective effect against sense of abandonment but a detrimental effect on concern about the risk for the patient to contract COVID-19. The only protective factor was mild dementia severity, which was associated with a lower risk of feeling isolated and abandoned; type of dementia, on the other hand, did not affect stress risk. Conclusion: Our results demonstrate the large prevalence of stress in family caregivers of patients with dementia during the COVID-19 pandemic and have identified both caregivers and situations at a higher risk of stress, which should be taken into account in the planning of interventions in support of quarantined families and patients.

Psychiatric disorders among hospitalized patients deceased with COVID-19 in Italy.

BACKGROUND: there is concern about the increased risk for SARS-CoV-2 infection, COVID-19 severe outcomes and disparity of care among patients with a psychiatric disorder (PD). Based on the Italian COVID-19 death surveillance, which collects data from all the hospitals throughout the country, we aimed to describe clinical features and care pathway of patients dying with COVID-19 and a preceding diagnosis of a PD. METHODS: in this cross-sectional study, the characteristics of a representative sample of patients, who have died with COVID-19 in Italian hospitals between February 21st and August 3rd 2020, were drawn from medical charts, described and analysed by multinomial logistic regression according to the recorded psychiatric diagnosis: no PD, severe PD (SPD) (i.e. schizophrenia and other psychotic disorders, bipolar and related disorders), common mental disorder (CMD) (i.e. depression without psychotic features, anxiety disorders). FINDINGS: the 4020 COVID-19 deaths included in the study took place in 365 hospitals across Italy. Out of the 4020 deceased patients, 84 (2•1%) had a previous SPD, 177 (4.4%) a CMD. The mean age at death was 78.0 (95%CI 77.6-78.3) years among patients without a PD, 71.8 (95%CI 69.3-72.0) among those with an SPD, 79.5 (95%CI 78.0-81.1) in individuals with a CMD. 2253 (61.2%) patients without a PD, 62 (73.8%) with an SPD, and 136 (78.2%) with a CMD were diagnosed with three or more non-psychiatric comorbidities.When we adjusted for clinically relevant variables, including hospital of death, we found that SPD patients died at a younger age than those without a PD (adjusted OR per 1 year increment 0.96; 95% CI 0.94-0.98). Women were significantly more represented among CMD patients compared to patients without previous psychiatric history (aOR 1.56; 95% CI 1.05-2.32). Hospital admission from long-term care facilities (LTCFs) was strongly associated with having an SPD (aOR 9.02; 95% CI 4.99-16.3) or a CMD (aOR 2.09; 95% CI 1.19-3.66). Comorbidity burden, fever, admission to intensive care and time from symptoms' onset to nasopharyngeal swab did not result significantly associated with an SPD or with a CMD in comparison to those without any PD. INTERPRETATION: even where equal treatment is in place, the vulnerability of patients with a PD may reduce their chance of recovering from COVID-19. The promotion of personalised therapeutic projects aimed at including people with PD in the community rather than in non-psychiatric LTCFs should be prioritised.

The Impact of COVID-19 Quarantine on Patients With Dementia and Family Caregivers: A Nation-Wide Survey.

INTRODUCTION: Previous studies showed that quarantine for pandemic diseases is associated with several psychological and medical effects. The consequences of quarantine for COVID-19 pandemic in patients with dementia are unknown. We investigated the clinical changes in patients with Alzheimer's disease and other dementias, and evaluated caregivers' distress during COVID-19 quarantine. METHODS: The study involved 87 Italian Dementia Centers. Patients with Alzheimer's Disease (AD), Dementia with Lewy Bodies (DLB), Frontotemporal Dementia (FTD), and Vascular Dementia (VD) were eligible for the study. Family caregivers of patients with dementia were interviewed by phone in April 2020, 45 days after quarantine declaration. Main outcomes were patients' changes in cognitive, behavioral, and motor symptoms. Secondary outcomes were effects on caregivers' psychological features. RESULTS: 4913 patients (2934 females, 1979 males) fulfilled the inclusion criteria. Caregivers reported a worsening in cognitive functions in 55.1% of patients, mainly in subjects with DLB and AD. Aggravation of behavioral symptoms was observed in 51.9% of patients. In logistic regression analysis, previous physical independence was associated with both cognitive and behavioral worsening (odds ratio 1.85 [95% CI 1.42-2.39], 1.84 [95% CI 1.43-2.38], respectively). On the contrary, pandemic awareness was a protective factor for the worsening of cognitive and behavioral symptoms (odds ratio 0.74 [95% CI 0.65-0.85]; and 0.72 [95% CI 0.63-0.82], respectively). Approximately 25.9% of patients showed the onset of new behavioral symptoms. A worsening in motor function was reported by 36.7% of patients. Finally, caregivers reported a high increase in anxiety, depression, and distress. CONCLUSION: Our study shows that quarantine for COVID-19 is associated with an acute worsening of clinical symptoms in patients with dementia as well as increase of caregivers' burden. Our findings emphasize the importance to implement new strategies to mitigate the effects of quarantine in patients with dementia.

The Italian national survey on Coronavirus disease 2019 epidemic spread in nursing homes.

INTRODUCTION: Residents in facilities such as nursing homes (NHs) are particularly vulnerable to Coronavirus disease 2019 (COVID-19). A national survey was carried out to collect information on the spreading and impact of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in nursing homes, and on how suspected and/or confirmed cases were managed. We carried out a survey between 25 March 2020 and 5 May 2020. MATERIALS AND METHODS: All Italian nursing homes either public or providing services both privately and within the NHS were included in the study. An on-line questionnaire was sent to 3292 nursing homes across all Italian regions. Nursing homes were also contacted by telephone to provide assistance in completing the questionnaire. RESULTS: A total of 1356 nursing homes voluntarily participated to the survey, hosting a total of 100,806 residents. Overall, 9154 residents died due to any cause from February 1 to the time when the questionnaire was completed (from March 25 to May 5). Of these, 7.4% had COVID-19 and 33.8% had flu-like symptoms, corresponding to a cumulative incidence of 0.7 and 3.1, respectively. Lack of personnel, difficulty in transferring patients to hospital or other facility, isolating residents with COVID-19, number of beds and geographical area were the main factor positively associated to the presence of COVID-19 in nursing homes. DISCUSSION: This survey showed the dissemination and impact of SARS-CoV-2 infection in Italian nursing homes and on how older and potentially chronically ill people residing in these long-term care facilities were managed.

Prevalence and clinical correlates of dementia among COVID-19-related deaths in Italy.

INTRODUCTION: We aimed at exploring the proportion of patients dying with COVID-19 and concomitant dementia in Italy, as well as their clinical characteristics and trajectories of care. METHODS: The proportion of COVID-19-related deaths occurring in people with dementia and the clinical characteristics of deceased individuals according to their dementia status were explored by considering the medical charts of a representative sample of patients deceased in Italian hospitals (n = 2621). RESULTS: A total of 415 individuals with dementia were identified in the study population, accounting for 15.8% of overall COVID-19-related deaths. Patients with dementia less frequently presented with cough, had lower chance of receiving supportive therapies and intensive care approaches, and showed a faster clinical worsening as compared with individuals with intact cognition. DISCUSSION: Dementia confers a relevant risk of adverse outcomes in case of SARS-CoV-2 infection and influences the clinical presentation, course and management of affected individuals.

Adverse Events in Italian Nursing Homes During the COVID-19 Epidemic: A National Survey.

Older people living in nursing homes (NHs) are particularly vulnerable in the ongoing COVID-19 pandemic, due to the high prevalence of chronic diseases and disabilities (e.g., dementia). The phenomenon of adverse events (AEs), intended as any harm or injury resulting from medical care or to the failure to provide care, has not yet been investigated in NHs during the pandemic. We performed a national survey on 3,292 NHs, either public or providing services both privately and within the national health system, out of the 3,417 NHs covering the whole Italian territory. An online questionnaire was addressed to the directors of each facility between March 24 and April 27, 2020. The list of NHs was provided by the Dementia Observatory, an online map of Italian services for people with dementia, which was one of the objectives of the implementation of the Italian National Dementia Plan. About 26% of residents in the Italian NHs for older people listed within the Dementia Observatory site had dementia. The objective of our study was to report the frequency of AEs that occurred during the months when SARS-CoV-2 spreading rate was at its highest in the Italian NHs and to identify which conditions and attributes were most associated with the occurrence of AEs by means of multivariate regression logistic analysis. Data are referred to 1,356 NHs that participated in the survey. The overall response rate was 41.2% over a time-period of six weeks (from March 24 to May 5). About one third of the facilities (444 out of 1,334) (33.3%) reported at least 1 adverse event, with a total of 2,000 events. Among the included NHs, having a bed capacity higher than the median of 60 beds (OR=1.57, CI95% 1.17-2.09; p=0.002), an observed increased in the use of psychiatric drugs (OR=1.80, CI95% 1.05-3.07; p=0.032), adopting physical restraint measures (OR=1.97, CI95% 1.47-2.64; p<0.001), residents hospitalized due to flu-like symptoms (OR =1.73, CI95% 1.28-2.32; p<0.001), and being located in specific geographic areas (OR=3.59, CI95% 1.81-7.08; OR = 2.90, CI95% 1.45-5.81 and OR = 4.02, CI05% 2.01-8.04 for, respectively, North-West, North-East and Centre vs South, p<0.001) were all factors positively associated to the occurrence of adverse events in the facility. Future recommendations for the management and care of residents in NHs during the COVID-19 pandemic should include specific statements for the most vulnerable populations, such as people with dementia.

Nonrespiratory Complications and Obesity in Patients Dying with COVID-19 in Italy.

OBJECTIVE: This study aimed to assess the impact of obesity on nonrespiratory complications in patients dying with coronavirus disease (COVID-19). METHODS: Medical charts of 3,694 of patients dying with COVID-19 in Italy were reviewed to extract information on demographics, preexisting comorbidities, and in-hospital complications leading to death. Multivariate logistic regressions were performed to assess the association of obesity with nonrespiratory complications. These analyses were adjusted for age, gender, and number of preexisting comorbidities. RESULTS: Obesity was present in 411/3,694 (11.1%) patients dying with COVID-19. Obesity was significantly associated with increased probability of experiencing acute renal failure (adjusted odds ratio [OR], 1.33; 95% CI: 1.04-1.71) and shock (adjusted OR, 1.54; 95% CI: 1.19-1.99). The associations of obesity with acute renal failure and shock were stronger in patients aged < 60 years (adjusted OR, 2.00; 95% CI: 1.09-3.67 and OR, 2.37; 95% CI 1.29-4.36) than in those aged 60 years or older (adjusted OR, 1.20; 95% CI: 0.90-1.60 and OR, 1.22; 95% CI: 0.91-1.65). CONCLUSIONS: In patients dying with COVID-19 in Italy, obesity is associated with an increased probability of nonrespiratory complications, particularly shock and acute renal failure. These associations seem stronger in younger than in older adults. Strategies should be put in place in patients with COVID-19 with obesity to prevent these complications.

Sex differences in clinical phenotype and transitions of care among individuals dying of COVID-19 in Italy.

BACKGROUND: Among the unknowns posed by the coronavirus disease 2019 (COVID-19) outbreak, the role of biological sex to explain disease susceptibility and progression is still a matter of debate, with limited sex-disaggregated data available. METHODS: A retrospective analysis was performed to assess if sex differences exist in the clinical manifestations and transitions of care among hospitalized individuals dying with laboratory-confirmed SARS-CoV-2 infection in Italy (February 27-June 11, 2020). Clinical characteristics and the times from symptoms' onset to admission, nasopharyngeal swab, and death were compared between sexes. Adjusted multivariate analysis was performed to identify the clinical features associated with male sex. RESULTS: Of the 32,938 COVID-19-related deaths that occurred in Italy, 3517 hospitalized and deceased individuals with COVID-19 (mean 78 ± 12 years, 33% women) were analyzed. At admission, men had a higher prevalence of ischemic heart disease (adj-OR = 1.76, 95% CI 1.39-2.23), chronic obstructive pulmonary disease (adj-OR = 1.7, 95% CI 1.29-2.27), and chronic kidney disease (adj-OR = 1.48, 95% CI 1.13-1.96), while women were older and more likely to have dementia (adj-OR = 0.73, 95% CI 0.55-0.95) and autoimmune diseases (adj-OR = 0.40, 95% CI 0.25-0.63), yet both sexes had a high level of multimorbidity. The times from symptoms' onset to admission and nasopharyngeal swab were slightly longer in men despite a typical acute respiratory illness with more frequent fever at the onset. Men received more often experimental therapy (adj-OR = 2.89, 95% CI 1.45-5.74) and experienced more likely acute kidney injury (adj-OR = 1.47, 95% CI 1.13-1.90). CONCLUSIONS: Men and women dying with COVID-19 had different clinical manifestations and transitions of care. Identifying sex-specific features in individuals with COVID-19 and fatal outcome might inform preventive strategies.